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Rafique S, Deeb Y, Ghanem F, Bhattarai M. Thrombotic Thrombocytopenic Purpura-Induced Cardiomyopathy and Troponin Clearance with Plasmapheresis: True or False Reassurance? Hosp Pharm 2025:00185787251328593. [PMID: 40125486 PMCID: PMC11926812 DOI: 10.1177/00185787251328593] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/25/2025]
Abstract
Thrombotic thrombocytopenic purpura (TTP) is a rare microangiopathic hemolytic anemia caused by a deficiency in the von Willebrand factor-cleaving protease ADAMTS13, resulting in the formation of microthrombi. TTP is associated with severe cardiovascular complications, such as myocardial infarction, congestive heart failure, arrhythmias, and cardiogenic shock, which can lead to a poor prognosis. Although plasmapheresis is the cornerstone of TTP treatment, it complicates the interpretation of cardiac biomarkers due to the rapid clearance of these markers from the bloodstream. We present the case of a 19-year-old African American female diagnosed with TTP who had critically elevated levels of high-sensitivity troponin (HS troponin). Notably, her HS troponin levels declined rapidly with ongoing plasmapheresis, underscoring the difficulties in interpreting cardiac biomarkers in TTP and the effects of treatment on these values. This case highlights the challenges in diagnosing and managing cardiovascular complications associated with TTP and their impact on patient prognosis.
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Affiliation(s)
- Soomal Rafique
- Southern Illinois University School of Medicine, Springfield, IL, USA
| | - Yara Deeb
- Southern Illinois University School of Medicine, Springfield, IL, USA
| | - Fares Ghanem
- Southern Illinois University School of Medicine, Springfield, IL, USA
| | - Mukul Bhattarai
- Southern Illinois University School of Medicine, Springfield, IL, USA
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Zhao G, Wang N, Zhang R, Zhang S. Comparability of the LDH measurement and analysis based on external quality assessment. Clin Chim Acta 2025; 569:120157. [PMID: 39870295 DOI: 10.1016/j.cca.2025.120157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2024] [Revised: 01/22/2025] [Accepted: 01/22/2025] [Indexed: 01/29/2025]
Abstract
BACKGROUND Lactate dehydrogenase (LDH) is a critical enzyme widely used in clinical diagnostics. However, variations in measurement systems can lead to inconsistent results, potentially impacting clinical decision-making. This study aimed to evaluate the comparability of lactate dehydrogenase measurements by comparing routine methods with the IFCC reference method, and to analyze the standardization status of LDH testing through external quality assessment (EQA). METHODS We analyzed 40 individual serum samples using four routine LD measurement systems: Siemens ADVIA 2400, Hitachi 7600/BioSino, Beckman AU5800, and Roche Cobas C501, alongside the IFCC reference method. The analytical quality specification (±6.4 %) was based on biological variation. Our study also included a comprehensive external quality assessment (EQA) program conducted by the Beijing Center for Clinical Laboratory (BCCL) over three years (2020, 2021, and 2023) to evaluate the consistency and reliability of LD measurements across different reagents. The acceptance limit is based on the requirement of desirable biological variability (±11.4 %). RESULTS All four measurement systems showed strong correlations with the IFCC reference method (r ≥ 0.98). Relative average deviations ranged from -5.23 % to 3.71 %, within the acceptable biological variation limit. External quality assessment revealed high pass rates (94.9 %-98.7 %) across reagent groups, with significant improvements observed in some reagent groups from 2020 to 2023.. CONCLUSIONS While the four LD measurement systems demonstrated good correlation with the IFCC reference method, some systems require further standardization. The study provides valuable insights into LD measurement accuracy and supports ongoing efforts to enhance laboratory testing comparability.
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Affiliation(s)
- Guanfei Zhao
- Department of Clinical Laboratory, Beijing Chaoyang Hospital, The Third Clinical Medical College of Capital Medical University, Beijing Center for Clinical Laboratories, No. 8 Gongti South Road, Chaoyang District, Beijing 100020, PR China
| | - Ning Wang
- Department of Clinical Laboratory, Beijing Chaoyang Hospital, The Third Clinical Medical College of Capital Medical University, Beijing Center for Clinical Laboratories, No. 8 Gongti South Road, Chaoyang District, Beijing 100020, PR China
| | - Rui Zhang
- Department of Clinical Laboratory, Beijing Chaoyang Hospital, The Third Clinical Medical College of Capital Medical University, Beijing Center for Clinical Laboratories, No. 8 Gongti South Road, Chaoyang District, Beijing 100020, PR China.
| | - Shunli Zhang
- Department of Clinical Laboratory, Beijing Chaoyang Hospital, The Third Clinical Medical College of Capital Medical University, Beijing Center for Clinical Laboratories, No. 8 Gongti South Road, Chaoyang District, Beijing 100020, PR China.
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Ostadi F, Anzali BC, Mehryar HR. Relationship between serum lactate dehydrogenase levels and prognosis in patients infected with omicron and delta variants of COVID-19: A cross-sectional study. Toxicol Rep 2023; 11:368-373. [PMID: 37868806 PMCID: PMC10589382 DOI: 10.1016/j.toxrep.2023.10.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Revised: 10/08/2023] [Accepted: 10/09/2023] [Indexed: 10/24/2023] Open
Abstract
Determining the prognosis of COVID-19 is crucial for understanding disease trends and developing effective treatment strategies, particularly for severe cases. However, there is currently insufficient evidence regarding the role of lactate dehydrogenase (LDH) in COVID-19 and its prognostic implications. This retrospective cross-sectional study analyzed data from all patients hospitalized at Urmia Imam Khomeini Hospital between September 2021 and March 2023 with a diagnosis of COVID-19 involving the Delta and Omicron variants. Patient information, including age, sex, duration of hospitalization, admission to the intensive care unit (ICU), strain type, and outcomes, was extracted. Exclusion criteria encompassed myocardial infarction, lung, liver, blood, skeletal muscle diseases, injury, neoplasm, pancreatitis, pregnancy, poisoning, unwillingness to participate in the study, and the use of ascorbic acid. A total of 609 patients with an average age of 54.80 years were included in this study. Among these patients, 56.3% were female, and the mortality rate was 20.7%. The serum LDH levels were significantly higher in patients who succumbed to the disease (P < 0.001), those requiring ICU admission (P < 0.001), and female patients (P = 0.02) compared to other groups. Furthermore, the LDH serum levels exhibited a strong significant correlation with the duration of hospitalization (r = -0.11, P = 0.007). The results revealed that there is a difference in the mean serum LDH levels between deceased patients and discharged patients (P < 0.001). The findings indicate that elevated serum LDH levels are associated with increased mortality, prolonged hospitalization, ICU admission, and infection with the Delta variant of COVID-19.
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Affiliation(s)
- Fatemeh Ostadi
- Department of medicine, School of medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Babak Choobi Anzali
- Emergency Medicine, Department of emergency Medicine, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Hamid Reza Mehryar
- Emergency Medicine, Department of emergency Medicine, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
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Bonnez Q, Sakai K, Vanhoorelbeke K. ADAMTS13 and Non-ADAMTS13 Biomarkers in Immune-Mediated Thrombotic Thrombocytopenic Purpura. J Clin Med 2023; 12:6169. [PMID: 37834813 PMCID: PMC10573396 DOI: 10.3390/jcm12196169] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Revised: 09/20/2023] [Accepted: 09/21/2023] [Indexed: 10/15/2023] Open
Abstract
Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare medical emergency for which a correct and early diagnosis is essential. As a severe deficiency in A Disintegrin And Metalloproteinase with ThromboSpondin type 1 repeats, member 13 (ADAMTS13) is the underlying pathophysiology, diagnostic strategies require timely monitoring of ADAMTS13 parameters to differentiate TTP from alternative thrombotic microangiopathies (TMAs) and to guide initial patient management. Assays for conventional ADAMTS13 testing focus on the enzyme activity and presence of (inhibitory) anti-ADAMTS13 antibodies to discriminate immune-mediated TTP (iTTP) from congenital TTP and guide patient management. However, diagnosis of iTTP remains challenging when patients present borderline ADAMTS13 activity. Therefore, additional biomarkers would be helpful to support correct clinical judgment. Over the last few years, the evaluation of ADAMTS13 conformation has proven to be a valuable tool to confirm the diagnosis of acute iTTP when ADAMST13 activity is between 10 and 20%. Screening of ADAMTS13 conformation during long-term patient follow-up suggests it is a surrogate marker for undetectable antibodies. Moreover, some non-ADAMTS13 parameters gained notable interest in predicting disease outcome, proposing meticulous follow-up of iTTP patients. This review summarizes non-ADAMTS13 biomarkers for which inclusion in routine clinical testing could largely benefit differential diagnosis and follow-up of iTTP patients.
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Affiliation(s)
- Quintijn Bonnez
- Department of Chemistry, KU Leuven Campus Kulak Kortrijk, 8500 Kortrijk, Belgium
| | - Kazuya Sakai
- Department of Chemistry, KU Leuven Campus Kulak Kortrijk, 8500 Kortrijk, Belgium
- Department of Blood Transfusion Medicine, Nara Medical University, Kashihara 634-8522, Japan
| | - Karen Vanhoorelbeke
- Department of Chemistry, KU Leuven Campus Kulak Kortrijk, 8500 Kortrijk, Belgium
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Sui J, Zheng L, Zheng XL. ADAMTS13 Biomarkers in Management of Immune Thrombotic Thrombocytopenic Purpura. Arch Pathol Lab Med 2023; 147:974-979. [PMID: 36223210 PMCID: PMC11033696 DOI: 10.5858/arpa.2022-0050-ra] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/24/2022] [Indexed: 11/06/2022]
Abstract
CONTEXT.— Immune thrombotic thrombocytopenic purpura (iTTP) is a rare but potentially fatal blood disorder resulting from acquired deficiency of plasma ADAMTS13, a metalloprotease that cleaves endothelium-derived ultralarge von Willebrand factor. Standard of care for iTTP including therapeutic plasma exchange, caplacizumab, and immunosuppressives, known as triple therapy, has led to a significant reduction in the disease-related mortality rate. The first International Society of Thrombosis and Haemostasis TTP guideline stresses the importance of having plasma ADAMTS13 activity testing in the algorithm for diagnosis and management of iTTP. However, the predictive role of assessing plasma ADAMTS13 activity and inhibitors or other ADAMTS13-related parameters in patients with acute iTTP and during remission has not been systematically evaluated. OBJECTIVE.— To review and assess the predictive values of testing plasma ADAMTS13 activity, antigen, and inhibitors or anti-ADAMTS13 immunoglobulin G at various stages of disease in outcomes of iTTP. DATA SOURCES.— Peer-reviewed publications and personal experience. CONCLUSIONS.— We conclude that assessing ADAMTS13 biomarkers is not only essential for establishing the initial diagnosis, but also crucial for risk stratification and the early detection of disease recurrence. This may guide therapeutic interventions during acute episodes and for long-term follow-up of iTTP patients.
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Affiliation(s)
- Jingrui Sui
- From the Department of Hematology, Yantai Yu Huang Ding Hospital Affiliated to Qingdao University, Shandong Province, China (Sui)
| | - Liang Zheng
- The Department of Pathology & Laboratory Medicine, University of Kansas Medical Center, Kansas City (L. Zheng, X. L. Zheng)
| | - X Long Zheng
- The Department of Pathology & Laboratory Medicine, University of Kansas Medical Center, Kansas City (L. Zheng, X. L. Zheng)
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Sakai K, Matsumoto M. Clinical Manifestations, Current and Future Therapy, and Long-Term Outcomes in Congenital Thrombotic Thrombocytopenic Purpura. J Clin Med 2023; 12:3365. [PMID: 37240470 PMCID: PMC10219024 DOI: 10.3390/jcm12103365] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 05/05/2023] [Accepted: 05/08/2023] [Indexed: 05/28/2023] Open
Abstract
Congenital thrombotic thrombocytopenic purpura (cTTP) is an extremely rare disease characterized by the severe deficiency of a disintegrin and metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13), caused by ADAMTS13 mutations. While ADAMTS13 supplementation by fresh frozen plasma (FFP) infusion immediately corrects platelet consumption and resolves thrombotic symptoms in acute episodes, FFP treatment can lead to intolerant allergic reactions and frequent hospital visits. Up to 70% of patients depend on regular FFP infusions to normalize their platelet counts and avoid systemic symptoms, including headache, fatigue, and weakness. The remaining patients do not receive regular FFP infusions, mainly because their platelet counts are maintained within the normal range or because they are symptom-free without FFP infusions. However, the target peak and trough levels of ADAMTS13 to prevent long-term comorbidity with prophylactic FFP and the necessity of treating FFP-independent patients in terms of long-term clinical outcomes are yet to be determined. Our recent study suggests that the current volumes of FFP infusions are insufficient to prevent frequent thrombotic events and long-term ischemic organ damage. This review focuses on the current management of cTTP and its associated issues, followed by the importance of upcoming recombinant ADAMTS13 therapy.
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Affiliation(s)
- Kazuya Sakai
- Department of Blood Transfusion Medicine, Nara Medical University, Kashihara 634-8522, Japan;
| | - Masanori Matsumoto
- Department of Blood Transfusion Medicine, Nara Medical University, Kashihara 634-8522, Japan;
- Department of Hematology, Nara Medical University, Kashihara 634-8521, Japan
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Omole AE, Ali A, Ogunniyi KE, Waqar D, Tobalesi O, Rahim O, Awosika A. A Case of Thrombotic Thrombocytopenic Purpura and ST-Elevation Myocardial Infarction: An Unusual Correlation. Cureus 2023; 15:e36039. [PMID: 37056547 PMCID: PMC10088566 DOI: 10.7759/cureus.36039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/12/2023] [Indexed: 03/14/2023] Open
Abstract
Thrombotic thrombocytopenic purpura (TTP) is a rare and potentially devastating blood disorder depicted by thrombocytopenia, fever, widespread small vessel hemolytic anemia, and neurological symptoms. The involvement of the renal and neurological systems is frequently reported in TTP; however, TTP-induced acute coronary syndrome is not widely reported. We describe a case of myocardial infarction induced by TTP in a patient who presented with the typical manifestation of acute coronary syndrome. Echocardiogram revealed a myocardial injury, and detailed investigations revealed increased levels of troponin I, lactate dehydrogenase, diminished levels of haptoglobin and von Willebrand factor-cleaving protease, and schistocytes on peripheral smear, suggestive of TTP-induced myocardial infarction. His condition was stabilized after commencing plasmapheresis, steroids, and rituximab. The initial steps in the management of this patient involve the prompt administration of steroids and the urgent start of plasmapheresis to increase platelet count.
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8
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Khalil F, Ali M, Ellithi M. Impact of Acute Coronary Syndrome on Clinical Outcomes in Patients With Thrombotic Thrombocytopenic Purpura. Cureus 2023; 15:e35878. [PMID: 37033586 PMCID: PMC10079805 DOI: 10.7759/cureus.35878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/06/2023] [Indexed: 03/09/2023] Open
Abstract
Thrombotic thrombocytopenic purpura (TTP) is a life-threatening clinical syndrome characterized by microangiopathy and a variable degree of end-organ ischemic damage. Cardiac involvement has been recognized as a major cause of mortality in these patients. In this study, we queried the National Inpatient Sample (NIS) for all patients hospitalized with thrombotic microangiopathy from 2002 to 2017, who also received plasma exchange (PLEX) during the same admission. A total of 6,214 patients with TTP were identified. We stratified patients based on whether or not they had acute coronary syndrome (ACS) during admission. ACS was documented in 6.3% of patients. Compared with patients without ACS, those with ACS were relatively older (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.02-1.03) and had a relatively higher prevalence of heart failure (OR, 2.02; 95% CI, 1.53-2.67) and coronary artery disease (OR, 2.69; 95% CI, 2.03-3.57). Certain complications were more prevalent in the ACS group including acute cerebrovascular accident (OR, 3.33; 95% CI, 2.94-3.78), acute heart failure (OR, 1.91; 95% CI, 1.67-2.19), acute kidney injury (OR, 1.76; 95% CI, 1.59-1.95), cardiogenic shock (OR, 2.15; 95% CI, 1.72-2.69), and respiratory failure (OR, 1.48; 95% CI, 1.32-1.66). Despite wider utilization of therapeutic plasmapheresis and improved supportive management of patients with TTP, associated morbidity and mortality remain significant. We demonstrate from this large retrospective cohort that ACS is an independent predictor of higher morbidity and mortality in TTP patients.
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9
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Nakakubo S, Unoki Y, Kitajima K, Terada M, Gatanaga H, Ohmagari N, Yokota I, Konno S. Serum Lactate Dehydrogenase Level One Week after Admission Is the Strongest Predictor of Prognosis of COVID-19: A Large Observational Study Using the COVID-19 Registry Japan. Viruses 2023; 15:v15030671. [PMID: 36992380 PMCID: PMC10058713 DOI: 10.3390/v15030671] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Revised: 02/18/2023] [Accepted: 03/01/2023] [Indexed: 03/06/2023] Open
Abstract
Clinical features of COVID-19 are diverse, and a useful tool for predicting clinical outcomes based on clinical characteristics of COVID-19 is needed. This study examined the laboratory values and trends that influence mortality in hospitalised COVID-19 patients. Data on hospitalised patients enrolled in a registry study in Japan (COVID-19 Registry Japan) were obtained. Patients with records on basic information, outcomes, and laboratory data on the day of admission (day 1) and day 8 were included. In-hospital mortality was set as the outcome, and associated factors were identified by multivariate analysis using the stepwise method. A total of 8860 hospitalised patients were included. The group with lactate dehydrogenase (LDH) levels >222 IU/L on day 8 had a higher mortality rate compared to the group with LDH levels ≤222 IU/L. Similar results were observed in subgroups formed by age, body mass index (BMI), underlying disease, and mutation type, except for those aged <50 years. When age, sex, BMI, underlying disease, and laboratory values on days 1 and 8 were tested for factors strongly associated with in-hospital mortality, LDH on day 8 was most strongly associated with mortality. LDH level on day 8 was the strongest predictor of in-hospital mortality in hospitalised COVID-19 patients, indicating its potential usefulness in post-treatment decision-making in severe COVID-19 cases.
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Affiliation(s)
- Sho Nakakubo
- Department of Respiratory Medicine, Faculty of Medicine, Hokkaido University, Sapporo 060-8638, Japan
- Correspondence: ; Tel.: +81-117-065911
| | - Yoko Unoki
- Department of Biostatistics, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan
| | - Koji Kitajima
- Centre for Clinical Sciences, National Centre for Global Health and Medicine, Tokyo 162-8655, Japan
| | - Mari Terada
- Centre for Clinical Sciences, National Centre for Global Health and Medicine, Tokyo 162-8655, Japan
- Disease Control and Prevention Centre, National Centre for Global Health and Medicine, Tokyo 162-8655, Japan
| | - Hiroyuki Gatanaga
- AIDS Clinical Centre, National Centre for Global Health and Medicine, Tokyo 162-8655, Japan
| | - Norio Ohmagari
- Disease Control and Prevention Centre, National Centre for Global Health and Medicine, Tokyo 162-8655, Japan
- AMR Clinical Reference Centre, National Centre for Global Health and Medicine, Tokyo 162-8655, Japan
| | - Isao Yokota
- Department of Biostatistics, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan
| | - Satoshi Konno
- Department of Respiratory Medicine, Faculty of Medicine, Hokkaido University, Sapporo 060-8638, Japan
- Institute for Vaccine Research and Development, Hokkaido University, Sapporo 060-8638, Japan
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Mohamed KH, Shiza ST, Samreen I, Agboola AA, Mohamed AS, Kalluru PKR, Haseeb M, Munawar RZ, Nasir H. Non-ST-Segment Elevation Myocardial Infarction As Initial Thrombotic Event of Thrombotic Thrombocytopenic Purpura: A Rare Challenging Case. Cureus 2023; 15:e36363. [PMID: 37082484 PMCID: PMC10112854 DOI: 10.7759/cureus.36363] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/18/2023] [Indexed: 04/22/2023] Open
Abstract
Thrombotic thrombocytopenic purpura (TTP) is a rare autoimmune and devastating blood disorder that results in micro-clots throughout the body, leading to tissue damage and organ dysfunction resulting in widespread microangiopathic hemolytic anemia, thrombocytopenia, fever, and neurological symptoms. TTP patients commonly manifest renal and neurological symptoms; however, cardiovascular involvement is not widely reported in the literature. We report a case of non-ST-segment elevation myocardial infarction (NSTEMI) as an initial manifestation of TTP. Although rare, TTP complications must be considered among other possible causes of unexpected thrombocytopenia during acute phase treatment of acute coronary syndrome because of high morbidity and mortality.
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Affiliation(s)
- Khalid H Mohamed
- Neurology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, GBR
| | - Saher T Shiza
- Internal Medicine, Deccan College of Medical Sciences, Hyderabad, IND
| | - Iqra Samreen
- Internal Medicine, Deccan College of Medical Sciences, Hyderabad, IND
| | | | | | | | - Muhammad Haseeb
- Internal Medicine, Allama Iqbal Medical College, Lahore, PAK
- Internal Medicine, Mount Sinai Hospital, Brooklyn, USA
| | | | - Hira Nasir
- Internal Medicine, Mayo Hospital, Lahore, PAK
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Chen J, He ZX, Wang FK. RETRACTED ARTICLE: Evaluation of ferritin level in COVID-19 patients and its inflammatory response. APPLIED NANOSCIENCE 2023; 13:3121. [PMID: 35136706 PMCID: PMC8812356 DOI: 10.1007/s13204-021-02115-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/11/2021] [Accepted: 09/24/2021] [Indexed: 01/08/2023]
Affiliation(s)
- Jing Chen
- Department of Clinical Laboratory, The 980th Hospital of PLA Joint Logistics Support Force, Shijiazhuang, 050082 China
| | - Zheng-Xin He
- Department of Clinical Laboratory, The 980th Hospital of PLA Joint Logistics Support Force, Shijiazhuang, 050082 China
| | - Fun-Kun Wang
- Department of Clinical Laboratory, The 980th Hospital of PLA Joint Logistics Support Force, Shijiazhuang, 050082 China
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12
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Gheith Z, Kilani A, Al-Taweel O. Unusual Presentation of Thrombotic Thrombocytopenic Purpura With Non-ST-Elevation Myocardial Infarction. Cureus 2022; 14:e29499. [DOI: 10.7759/cureus.29499] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/23/2022] [Indexed: 11/05/2022] Open
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13
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Scully M, Dutt T, Lester W, Farrington E, Lockwood S, Perry R, Holmes S. Unmet needs in the management of immune-mediated thrombotic thrombocytopenic purpura and the potential role of caplacizumab in the UK-A modified-Delphi study. EJHAEM 2022; 3:619-627. [PMID: 36051029 PMCID: PMC9422011 DOI: 10.1002/jha2.435] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 03/18/2022] [Accepted: 03/23/2022] [Indexed: 06/15/2023]
Abstract
Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is an ultra-rare, blood-clotting disorder. Management historically relies on plasma exchange and immunosuppression; however, a 10%-20% mortality rate is still observed. Caplacizumab binds to von Willebrand factor and directly inhibits platelet aggregation; addition of caplacizumab to historical treatment induced faster resolution of platelet count in clinical trials. In 2019, a modified-Delphi study was conducted with UK experts, to develop consensus statements on management of acute TTP and the potential role of caplacizumab. An unmet need was acknowledged, and areas requiring improvement included: time to diagnosis and treatment initiation; time to platelet normalisation (TTPN) during which patients remain at risk of persistent microvascular thrombosis and organ damage; and incidence of subsequent exacerbations and relapses. Caplacizumab addition to historical treatment within 24 h (after confirmatory ADAMTS13 [a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13] assay) would significantly reduce TTPN, which directly influences acute outcomes, with manageable bleeding risk and reduced burden on healthcare systems. Expert panellists agree that poor outcomes in iTTP largely result from failure to rapidly control microvascular thrombosis. Use of caplacizumab during a confirmed iTTP episode could offer better control and may plausibly improve long-term outcomes. However, this consensus must be validated with further clinical trials and robust real-world evidence.
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Affiliation(s)
- Marie Scully
- Department of HaematologyUniversity College London HospitalLondonUK
| | - Tina Dutt
- Liverpool University Hospitals, NHS Foundation TrustLiverpoolUK
| | - Will Lester
- Centre for Clinical HaematologyNHS Foundation TrustUniversity Hospitals BirminghamBirminghamUK
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Severe Thrombotic Thrombocytopenic Purpura (TTP) with Organ Failure in Critically Ill Patients. J Clin Med 2022; 11:jcm11041103. [PMID: 35207375 PMCID: PMC8874413 DOI: 10.3390/jcm11041103] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Revised: 02/07/2022] [Accepted: 02/17/2022] [Indexed: 01/27/2023] Open
Abstract
Thrombotic thrombocytopenic purpura (TTP) is a multiorgan disorder. Organ dysfunction occurs as a consequence of widespread microvascular thrombosis, especially in the heart, brain and kidney, causing transient or partial occlusion of vessels, resulting in organ ischemia. Intensive care unit (ICU) admission varies between 40% and 100% of patients with TTP, either because of severe organ failure or in order to initiate emergency plasma exchange (PEx). Severe neurologic manifestations and cardiac involvement have been associated with higher mortality. Acute kidney injury, although usually less severe than that in hemolytic and uremic syndrome, is common during TTP. Initial management in the ICU should always be considered in TTP patients. The current treatment of TTP in the acute phase is based on urgent PEx, combined with corticosteroid therapy, B-cell-targeted immunotherapy, rituximab and inhibition of the interaction between ultra-large Von Willebrand factor multimers and platelets, using caplacizumab, a monoclonal antibody. ICU management permits close monitoring and the rapid introduction of life-sustaining therapies. This review details the epidemiology of TTP in the ICU, organ failures of critically ill patients with TTP, and the initial management of TTP patients in the ICU.
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Ghodsi S, Jenab Y, Mohebi M, Kamranzadeh H, Mohammadi Z. ST-Segment-Elevation Myocardial Infarction Unmasking Underlying Systemic Lupus Erythematosus or Representing Thrombotic Thrombocytopenic Purpura? Report of a Challenging Case. J Tehran Heart Cent 2022; 16:84-88. [PMID: 35082877 PMCID: PMC8742866 DOI: 10.18502/jthc.v16i2.7391] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2020] [Accepted: 03/24/2021] [Indexed: 11/24/2022] Open
Abstract
Thrombotic thrombocytopenic purpura (TTP) is a multisystem disorder that frequently manifests itself with renal and neurological involvements. Cardiac involvement, however, has been rarely reported. In this report, we present a rare case of acquired TTP with acute myocardial infarction (AMI) as the initial manifestation. Although AMI was successfully managed by percutaneous coronary intervention, the patient developed hemolytic anemia, fever, marked thrombocytopenia, oliguria, and renal dysfunction, requiring treatment with plasma exchange and corticosteroids. TTP, albeit extremely rare, should be considered in cases with unexpected thrombocytopenia during acute-phase treatment for AMI as it can be highly lethal if not treated immediately.
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Affiliation(s)
- Saeed Ghodsi
- Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Yaser Jenab
- Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Mehrnaz Mohebi
- Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Hosein Kamranzadeh
- Hematology-Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Zohre Mohammadi
- Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
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16
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Cui X, Wang S, Jiang N, Li Z, Li X, Jin M, Yang B, Jia N, Hu G, Liu Y, He Y, Liu Y, Zhao S, Yu Q. Establishment of prediction models for COVID-19 patients in different age groups based on Random Forest algorithm. QJM 2022; 114:795-801. [PMID: 34668535 DOI: 10.1093/qjmed/hcab268] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2021] [Revised: 09/21/2021] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) has rapidly become a global pandemic. Age is an independent factor in death from the disease, and predictive models to stratify patients according to their mortality risk are needed. AIM To compare the laboratory parameters of the younger (≤70) and the elderly (>70) groups, and develop death prediction models for the two groups according to age stratification. DESIGN A retrospective, single-center observational study. METHODS This study included 437 hospitalized patients with laboratory-confirmed COVID-19 from Tongji Hospital in Wuhan, China, 2020. Epidemiological information, laboratory data and outcomes were extracted from electronic medical records and compared between elderly patients and younger patients. First, recursive feature elimination (RFE) was used to select the optimal subset. Then, two random forest (RF) algorithms models were built to predict the prognoses of COVID-19 patients and identify the optimal diagnostic predictors for patients' clinical prognoses. RESULTS Comparisons of the laboratory data of the two age groups revealed many different laboratory indicators. RFE was used to select the optimal subset for analysis, from which 11 variables were screened out for the two groups. The RF algorithm were built to predict the prognoses of COVID-19 patients based on the best subset, and the area under ROC curve (AUC) of the two groups is 0.874 (95% CI: 0.833-0.915) and 0.842 (95% CI: 0.765-0.920). CONCLUSION Two prediction models for COVID-19 were developed in the patients with COVID-19 based on random forest algorithm, which provides a simple tool for the early prediction of COVID-19 mortality.
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Affiliation(s)
- X Cui
- From the Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, 1163 Xinmin Street, Changchun 130021, China
| | - S Wang
- Department of Intensive Care Unit, China-Japan Union Hospital of Jilin University, Changchun 130000, China
| | - N Jiang
- Department of Emergency, China-Japan Union Hospital of Jilin University, 126 Xiantai Street, Changchun 130000, China
| | - Z Li
- From the Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, 1163 Xinmin Street, Changchun 130021, China
| | - X Li
- From the Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, 1163 Xinmin Street, Changchun 130021, China
| | - M Jin
- From the Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, 1163 Xinmin Street, Changchun 130021, China
| | - B Yang
- Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology,1095 Jiefang Road, Wuhan 430000, China
| | - N Jia
- From the Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, 1163 Xinmin Street, Changchun 130021, China
| | - G Hu
- From the Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, 1163 Xinmin Street, Changchun 130021, China
| | - Y Liu
- From the Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, 1163 Xinmin Street, Changchun 130021, China
| | - Y He
- From the Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, 1163 Xinmin Street, Changchun 130021, China
| | - Y Liu
- From the Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, 1163 Xinmin Street, Changchun 130021, China
| | - S Zhao
- Department of Emergency, China-Japan Union Hospital of Jilin University, 126 Xiantai Street, Changchun 130000, China
| | - Q Yu
- From the Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, 1163 Xinmin Street, Changchun 130021, China
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17
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Long B, Bridwell RE, Manchanda S, Gottlieb M. Evaluation and Management of Thrombotic Thrombocytopenic Purpura in the Emergency Department. J Emerg Med 2021; 61:674-682. [PMID: 34518045 DOI: 10.1016/j.jemermed.2021.07.045] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 07/15/2021] [Accepted: 07/25/2021] [Indexed: 01/28/2023]
Abstract
BACKGROUND Thrombotic thrombocytopenic purpura (TTP) is a dangerous condition that can be misdiagnosed in the emergency department. OBJECTIVE The purpose of this narrative review article is to provide a summary of the background, pathophysiology, diagnosis, and management of TTP, with a focus on emergency clinicians. DISCUSSION TTP is a disorder with microangiopathic hemolytic anemia, severe thrombocytopenia, and multiorgan ischemic injury. It may be acquired or hereditary, and is caused by a reduced amount or function of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13), which is an enzyme involved in cleaving von Willebrand factor. The classic presentation of TTP includes fever, neurologic abnormalities, thrombocytopenia with purpura, microangiopathic hemolytic anemia, and acute renal injury. However, < 7% of cases have all of these findings present. Testing should include a complete blood count, complete metabolic panel, blood smear, coagulation panel, fibrinogen, D-dimer, lactate dehydrogenase, ADAMTS13 level, troponin, human immunodeficiency virus assessment, urinalysis, pregnancy test as appropriate, and electrocardiogram. Management includes hematology consultation if available, plasma exchange and corticosteroids, and treatment of end-organ complications. All patients require admission for treatment and close monitoring. CONCLUSION TTP is a potentially dangerous medical condition requiring rapid diagnosis and management. It is essential for emergency clinicians to know how to diagnose and treat this disorder.
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Affiliation(s)
- Brit Long
- Department of Emergency Medicine, Brooke Army Medical Center, Fort Sam Houston, Texas
| | - Rachel E Bridwell
- Department of Emergency Medicine, Brooke Army Medical Center, Fort Sam Houston, Texas
| | - Shivon Manchanda
- Department of Emergency Medicine, Rush University Medical Center, Chicago, Illinois
| | - Michael Gottlieb
- Department of Emergency Medicine, Rush University Medical Center, Chicago, Illinois
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18
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Holmes S, Podger L, Bottomley C, Rzepa E, Bailey KMA, Chandler F. Survival after acute episodes of immune-mediated thrombotic thrombocytopenic purpura (iTTP) - cognitive functioning and health-related quality of life impact: a descriptive cross-sectional survey of adults living with iTTP in the United Kingdom. ACTA ACUST UNITED AC 2021; 26:465-472. [PMID: 34238132 DOI: 10.1080/16078454.2021.1945236] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
OBJECTIVES Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is an ultra-rare life-threatening thrombotic microangiopathy affecting adults with unpredictable disease onset and acute presentation. This study aimed to describe the health-related quality of life (HRQoL), cognitive functioning and work productivity of survivors following acute episode(s) of iTTP in the United Kingdom (UK). METHODS An online survey was developed in collaboration with the TTP Network. Descriptive statistics were calculated for the health questionnaire Short Form Survey-36 Version 2 (SF-36v2), the Hospital Anxiety and Depression Score (HADS), the PROMIS Cognitive Function Abilities Subset - Short Form 6a (PROMIS CFAS - SF6a), and the Work Productivity and Activity Index: Specific Health Problem (WPAI-SHP), along with several iTTP-specific bespoke questions. RESULTS Fifty participants were recruited between July-November 2019. The mean (standard deviation [SD]) standardized SF-36v2 physical and mental component scores were 42.16 (9.59) and 33.61 (12.34), lower than population norms. The mean (SD) standardized PROMIS CFAS - SF6a score was 39.69 (7.86), lower than population norms. HADS mean (SD) scores of 12.18 (3.14) and 11.78 (2.36) indicated moderate levels of anxiety and depression, respectively. Of those employed (58%), approximately 42.73% of participants reported work productivity loss due to their iTTP. Participants also reported experiencing flashbacks, fatigue interference in family, social and intimate life, and fears of relapse. DISCUSSION AND CONCLUSION Regardless of recency of the last acute episode, participant scores signified impairments in all domains. Remission from an acute episode of disease does not signify the conclusion of care, but rather the requirement for long-term healthcare particularly focused on psychological support.
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19
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Balasubramaniyam N, Yandrapalli S, Kolte D, Pemmasani G, Janakiram M, Frishman WH. Cardiovascular Complications and Their Association With Mortality in Patients With Thrombotic Thrombocytopenic Purpura. Am J Med 2021; 134:e89-e97. [PMID: 32687814 DOI: 10.1016/j.amjmed.2020.06.020] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2020] [Revised: 06/09/2020] [Accepted: 06/10/2020] [Indexed: 02/05/2023]
Abstract
BACKGROUND Despite widespread availability of plasmapheresis, the mortality in thrombotic thrombocytopenic purpura remains high. Cardiovascular complications have been reported as an important cause of morbidity in these patients. The burden and prognostic implications of these complications have not been well studied. We analyzed the rates of cardiovascular complications in thrombotic thrombocytopenic purpura, temporal trends, and studied its impact on in-hospital mortality. METHODS We analyzed the National Inpatient Sample (NIS) from January 2005 to September 2015 to identify adult patients with thrombotic thrombocytopenic purpura. This group was further refined by excluding patients who did not receive therapeutic plasmapheresis, and other conditions that can mimic thrombotic thrombocytopenic purpura. We identified the age- and sex-stratified rates of cardiac arrhythmias, cardiac conduction system disorders, heart failure, acute coronary syndrome, myocarditis, pericarditis, takotsubo cardiomyopathy, cardiogenic shock, cardiac arrest, and stroke. We also compared in-hospital mortality with and without cardiovascular complications. RESULTS Among 15,054 thrombotic thrombocytopenic purpura hospitalizations (mean age 46.4 years, 69% in the 18- to 54-age group, 66.2% women, and 42.9% white), a cardiovascular complication was observed in 3802 (25.3%) hospitalizations. The following cardiovascular complications were identified: stroke (10.4%), heart failure (8.3%), acute coronary syndrome (6.4%), atrial tachyarrhythmia (5.9%), ventricular tachyarrhythmia (2.0%), cardiogenic shock (0.5%), takotsubo cardiomyopathy (0.1%), atrioventricular block (0.2%), myocarditis or pericarditis (0.3), and cardiac arrest (1.9%). Rates of several cardiovascular complications were significantly higher in patients 55 years or older compared to a younger age group, whereas males had higher rates of acute coronary syndrome and tachyarrhythmias compared to females. Overall, the cardiovascular complication rate was stable during the study period. The presence of a major cardiovascular complication was associated with a significantly higher in-hospital mortality (19.7%) as compared with no major cardiovascular complication (4.1%) (adjusted odds ratio 2.09, 95% confidence interval 1.41-3.09, P <0.001). Results were generally consistent in age and sex subgroups. CONCLUSION Cardiovascular complications were frequently observed at a rate of 1 in 4 in patients hospitalized for thrombotic thrombocytopenic purpura and were associated with substantially higher in-hospital mortality. These findings underscore the need to promptly identify and treat these complications to improve outcomes.
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Affiliation(s)
| | - Srikanth Yandrapalli
- Division of Cardiology, Westchester Medical Center and New York Medical College, Valhalla, NY
| | - Dhaval Kolte
- Division of Cardiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA
| | | | - Murali Janakiram
- Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN
| | - William H Frishman
- Department of Medicine, Westchester Medical Center and New York Medical College, Valhalla, NY
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20
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Pollissard L, Shah A, Punekar RS, Petrilla A, Pham HP. Burden of illness among Medicare and non-Medicare US populations with acquired thrombotic thrombocytopenic purpura. J Med Econ 2021; 24:706-716. [PMID: 33904347 DOI: 10.1080/13696998.2021.1922262] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/30/2022]
Abstract
BACKGROUND Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare hematologic disorder that can lead to serious life-threatening medical complications. OBJECTIVE The aim of this study was to describe aTTP-related hospital resource utilization, cost, complications, and overall survival among US Medicare and non-Medicare populations following aTTP episodes prior to the US approval of caplacizumab. METHODS This retrospective study utilized administrative claims data for Medicare Fee-for-Service (FFS) beneficiaries (100% sample) and a sample of commercial, managed Medicaid [MM], Medicare Advantage [MA] plan members from the Inovalon MORE2 Registry. aTTP patients ages 18+ were identified between 2010 and 2018 using a published validated algorithm: ≥1 hospitalization for thrombotic microangiopathy + therapeutic plasma exchange (TPE). 2,279 patients were identified; 65.2% were enrolled in Medicare FFS, 13.6% in commercial, 15.7% in MM, and 5.4% in MA. Mean hospitalization days for aTTP index episode ranged between 12 and 17 days; ∼60% of patients required intensive care. Mean payments for index hospitalization varied by payer [Medicare FFS: $29,024; MA: $12,860; commercial: $9,996 and MM: $10,470]. Among FFS patients, 15.7% died during initial hospitalization and 21.0% died within first 30 days of the event. During follow-up, 11.6-19.6% experienced aTTP-related exacerbation. Incidence rate of relapse and complications per 100 person-years was 5.6 [Medicare FFS: 3.6; MA: 8.7; commercial: 10.4 and MM: 14.7] and 16.7 [FFS: 15.5; MA: 20.5; commercial: 21.7 and MM: 19.1], respectively. Among Medicare patients with and without aTTP, mortality risk was 2.9 (95 % CI: 2.4-3.4) times higher for aTTP vs. non-aTTP patients. CONCLUSION This is the first real-world study evaluating burden of illness among aTTP patients in the US across payer types. Despite being treated with TPE, patients with aTTP have lower survival rates in comparison to a matched cohort without aTTP. These findings highlight the need for more effective and novel therapies to reduce disease burden for this population.Key pointsIn US Medicare and managed care populations with aTTP between 2010 and 2018, aTTP can lead to significant utilization of ICU services due to clinical complications, and/or relapse following hospital discharge.Despite treatment with therapeutic plasma exchange, acute mortality remains high (15.7%) indicating the need for more effective and novel treatments.
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Affiliation(s)
| | | | | | | | - Huy P Pham
- National Marrow Donor Program, Seattle, WA, USA
- Department of Pathology, University of Southern California, Los Angeles, CA, USA
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21
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Henry BM, Aggarwal G, Wong J, Benoit S, Vikse J, Plebani M, Lippi G. Lactate dehydrogenase levels predict coronavirus disease 2019 (COVID-19) severity and mortality: A pooled analysis. Am J Emerg Med 2020; 38:1722-1726. [PMID: 32738466 PMCID: PMC7251362 DOI: 10.1016/j.ajem.2020.05.073] [Citation(s) in RCA: 353] [Impact Index Per Article: 70.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Revised: 05/20/2020] [Accepted: 05/20/2020] [Indexed: 02/06/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) infection has now reached a pandemic state, affecting more than a million patients worldwide. Predictors of disease outcomes in these patients need to be urgently assessed to decrease morbidity and societal burden. Lactate dehydrogenase (LDH) has been associated with worse outcomes in patients with viral infections. In this pooled analysis of 9 published studies (n = 1532 COVID-19 patients), we evaluated the association between elevated LDH levels measured at earliest time point in hospitalization and disease outcomes in patients with COVID-19. Elevated LDH levels were associated with a ~6-fold increase in odds of developing severe disease and a ~16-fold increase in odds of mortality in patients with COVID-19. Larger studies are needed to confirm these findings.
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Affiliation(s)
- Brandon Michael Henry
- Cardiac Intensive Care Unit, The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
| | - Gaurav Aggarwal
- Department of Medicine, Jersey City Medical Center, Jersey City, NJ, USA
| | - Johnny Wong
- College of Medicine, SUNY Downstate Health Sciences University, New York, USA
| | - Stefanie Benoit
- Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, OH, USA; Department of Pediatrics, College of Medicine, University of Cincinnati, OH, USA
| | - Jens Vikse
- Department of Clinical immunology, Stavanger University Hospital, Stavanger, Norway
| | - Mario Plebani
- Department of Lab Medicine, University Hospital, Padova, Italy
| | - Giuseppe Lippi
- Section of Clinical Biochemistry, Department of Neuroscience, Biomedicine and Movement, University of Verona, Verona, Italy
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22
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Agosti P, Mancini I, Gianniello F, Bucciarelli P, Artoni A, Ferrari B, Pontiggia S, Trisolini SM, Facchini L, Carbone C, Peyvandi F. Prevalence of the age-related diseases in older patients with acquired thrombotic thrombocytopenic purpura. Eur J Intern Med 2020; 75:79-83. [PMID: 32201091 DOI: 10.1016/j.ejim.2020.01.024] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Revised: 01/27/2020] [Accepted: 01/29/2020] [Indexed: 11/19/2022]
Abstract
BACKGROUND The prevalence of older patients with acquired thrombotic thrombocytopenic purpura (TTP) is increasing. There is scarce information on the prevalence of multimorbidity, polypharmacy and age-related diseases in aging TTP patients. This study aimed to evaluate the prevalence of multimorbidity and polypharmacy in a population of acquired TTP patients aged 65 years or more compared with a group of age-matched controls. METHODS Acquired TTP patients enrolled in the Milan TTP registry from December 1st 1999 to March 31th 2018 and aged 65 years or more at the date of last follow-up were evaluated. Controls were Italian healthy individuals recruited from 2006 to March 31th 2018 among friends and non-consanguineous relatives of patients tested for thrombophilia screening at the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center of Milan. RESULTS 36 TTP patients and 127 age-matched controls were included. Compared with controls, TTP patients had a higher prevalence of multimorbidity and polypharmacy. They also showed a higher prevalence of autoimmune diseases, osteoporosis and arterial hypertension and were more chronically treated with corticosteroids and antiplatelets for primary cardiovascular prevention. All these results were confirmed after adjusting for sex. Compared with the general elderly population, TTP patients showed a higher prevalence of ischemic heart disease and stroke. CONCLUSIONS Our findings suggest that a careful comprehensive geriatric assessment of acquired TTP patients is necessary. It is important to look for other autoimmune diseases and such age-related comorbidities as osteoporosis, arterial hypertension, ischemic heart disease and cerebrovascular disease.
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Affiliation(s)
- Pasquale Agosti
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano,Via Pace 9, Milan, 20122, Italy
| | - Ilaria Mancini
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano,Via Pace 9, Milan, 20122, Italy
| | - Francesca Gianniello
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, and Fondazione Luigi Villa, Milan, Italy
| | - Paolo Bucciarelli
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, and Fondazione Luigi Villa, Milan, Italy
| | - Andrea Artoni
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, and Fondazione Luigi Villa, Milan, Italy
| | - Barbara Ferrari
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, and Fondazione Luigi Villa, Milan, Italy
| | - Silvia Pontiggia
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, and Fondazione Luigi Villa, Milan, Italy
| | - Silvia Maria Trisolini
- Hematology, Department of Translational and Precision Medicine, Sapienza University, Rome, Italy
| | - Luca Facchini
- Hematology Unit, Azienda Unità Sanitaria Locale - IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Cecilia Carbone
- UO Ematologia, ASST Spedali Civili di Brescia, Brescia, Italy
| | - Flora Peyvandi
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano,Via Pace 9, Milan, 20122, Italy; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, and Fondazione Luigi Villa, Milan, Italy.
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23
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Gómez-De León A, Villela-Martínez LM, Yáñez-Reyes JM, Gómez-Almaguer D. Advances in the treatment of thrombotic thrombocytopenic purpura: repurposed drugs and novel agents. Expert Rev Hematol 2020; 13:461-470. [DOI: 10.1080/17474086.2020.1750361] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Affiliation(s)
- Andrés Gómez-De León
- Hematology Department, Universidad Autónoma de Nuevo León, Facultad de Medicina y Hospital Universitario ‘Dr. José Eleuterio González’, Monterrey, México
| | - Luis Mario Villela-Martínez
- Centro Médico “Dr. Ignacio Chavez”. ISSSTESON, Hermosillo, México
- Universidad del Valle de México. Campus Hermosillo, Hermosillo, México
| | - José Miguel Yáñez-Reyes
- Hematology Department, Universidad Autónoma de Nuevo León, Facultad de Medicina y Hospital Universitario ‘Dr. José Eleuterio González’, Monterrey, México
| | - David Gómez-Almaguer
- Hematology Department, Universidad Autónoma de Nuevo León, Facultad de Medicina y Hospital Universitario ‘Dr. José Eleuterio González’, Monterrey, México
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Miesbach W, Menne J, Bommer M, Schönermarck U, Feldkamp T, Nitschke M, Westhoff TH, Seibert FS, Woitas R, Sousa R, Wolf M, Walzer S, Schwander B. Incidence of acquired thrombotic thrombocytopenic purpura in Germany: a hospital level study. Orphanet J Rare Dis 2019; 14:260. [PMID: 31730475 PMCID: PMC6858672 DOI: 10.1186/s13023-019-1240-0] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2019] [Accepted: 10/29/2019] [Indexed: 12/12/2022] Open
Abstract
Background Acquired thrombotic thrombocytopenic Purpura (aTTP) is a life-threatening ultra-orphan disease with a reported annual incidence between 1.5 and 6.0 cases per million in Europe and mainly affecting otherwise young and healthy adults aged 40 years on average. The goal of this study was to assess the incidence of aTTP in Germany. Methods A systematic review was performed to determine the published evidence on the aTTP epidemiology in Germany. To obtain additional evidence on the proportion of aTTP cases within the national Thrombotic Microangiopathy (TMA) population a hospital-level study was performed, using a retrospective data collection approach. Diagnosis of aTTP was confirmed if ADAMTS13 level were < 10% and/or the medical records explicitly mentioned aTTP diagnosis. The aggregated hospital data were then projected to the national level using logistic regression techniques. Results The systematic literature search did not provide incidence estimates of aTTP in Germany. Eight centers (≈27% of the top 30 TMA hospitals) delivered data according to a predefined data collection form. On average (year 2014–2016) a total number of 172 aTTP episodes per year was projected (95% confidence interval [95%CI]: 132–212). The majority were newly diagnosed aTTP cases (n = 121; 95%CI: 105–129), and 51 were recurrent aTTP cases (95%CI: 27–84). The average annual projected incidence (year 2014–2016) of aTTP episodes was 2.10 per million inhabitants in Germany (95%CI: 1.60–2.58). Conclusions The determined annual incidence of newly diagnosed aTTP cases and the overall annual incidence of aTTP episodes in Germany confirm the ultra-orphan character of aTTP. An external validation against international registries (France, UK and USA) shows that our findings are quite comparable with those international incidence rates.
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Affiliation(s)
- Wolfgang Miesbach
- Universitätsklinikum Frankfurt, Medizinische Klinik II / Institut für Transfusionsmedizin und Immunhämatologie, Frankfurt, Germany.
| | - Jan Menne
- Medizinische Hochschule Hannover, Klinik für Nieren- und Hochdruckerkrankungen, Hannover, Germany
| | - Martin Bommer
- Alb-Fils Kliniken Göppingen, Klinik für Hämatologie, Onkologie und Infektionskrankheiten, Göppingen, Germany
| | - Ulf Schönermarck
- Klinikum der Universität München - Medizinische Klinik und Poliklinik IV, Nephrologisches Zentrum, München, Germany
| | - Thorsten Feldkamp
- Klinik für Innere Medizin IV - Universitätsklinikum Schleswig Holstein, Nieren- und Hochdruckkrankheiten, Kiel, Germany
| | - Martin Nitschke
- Medizinische Klinik I - Universitätsklinikum Schleswig Holstein, Nephrologie & Transplantation, Lübeck, Germany
| | - Timm H Westhoff
- Medizinische Klinik I - Universitätsklinikum Marien Hospital Herne, Ruhr-Universität Bochum, Herne, Germany
| | - Felix S Seibert
- Medizinische Klinik I - Universitätsklinikum Marien Hospital Herne, Ruhr-Universität Bochum, Herne, Germany
| | - Rainer Woitas
- Medizinische Klinik und Poliklinik I - Universitätsklinikum Bonn, Bonn, Germany
| | - Rui Sousa
- Ablynx a Sanofi Company, Medical Affairs, Zwijnaarde, Belgium
| | - Michael Wolf
- Ablynx a Sanofi Company, Medical Affairs, Zwijnaarde, Belgium
| | - Stefan Walzer
- MArS - Market Access & Pricing Strategy GmbH, Weil am Rhein, Germany
| | - Björn Schwander
- AHEAD GmbH, Agency for Health Economic Assessment and Dissemination, Lörrach, Germany
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Maqsood MH, Rubab K, Maqsood MZ. Clinical Efficacy and Safety Profile of Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura. Cureus 2019; 11:e5263. [PMID: 31576256 PMCID: PMC6764618 DOI: 10.7759/cureus.5263] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Thrombotic thrombocytopenic purpura (TTP) is usually defined as microangiopathy characterized by low platelet count and low red blood cell count, i.e., hemolytic anemia. It can either be acquired or immune-mediated. TTP requires quick diagnostic identification and emergent management. According to the evidence-based guidelines, the recommended therapy is plasma exchange and immunosuppression. Caplacizumab is used alongside the standard recommended therapy. Caplacizumab is a monoclonal antibody (Mab) that binds to von Willebrand factor (VWF). This prevents A1 VWF to bind platelet glycoprotein 1b receptor. The recommended dosage for this drug is 10mg. At the start, 10mg intravenous (IV) dose is given before plasma exchange, followed by daily 10mg subcutaneous (SC) dose after plasma exchange. Moreover, the SC dose is continued even after the daily plasma exchange is stopped. This review aims to consolidate findings related to the efficacy of this recently approved drug.
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Affiliation(s)
| | - Kinza Rubab
- Internal Medicine, King Edward Medical University / Mayo Hospital, Lahore, PAK
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26
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Latifi Y, Moccetti F, Wu M, Xie A, Packwood W, Qi Y, Ozawa K, Shentu W, Brown E, Shirai T, McCarty OJ, Ruggeri Z, Moslehi J, Chen J, Druker BJ, López JA, Lindner JR. Thrombotic microangiopathy as a cause of cardiovascular toxicity from the BCR-ABL1 tyrosine kinase inhibitor ponatinib. Blood 2019; 133:1597-1606. [PMID: 30692122 PMCID: PMC6450432 DOI: 10.1182/blood-2018-10-881557] [Citation(s) in RCA: 70] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2018] [Accepted: 01/16/2019] [Indexed: 01/13/2023] Open
Abstract
The third-generation tyrosine kinase inhibitor (TKI) ponatinib has been associated with high rates of acute ischemic events. The pathophysiology responsible for these events is unknown. We hypothesized that ponatinib produces an endothelial angiopathy involving excessive endothelial-associated von Willebrand factor (VWF) and secondary platelet adhesion. In wild-type mice and ApoE-/- mice on a Western diet, ultrasound molecular imaging of the thoracic aorta for VWF A1-domain and glycoprotein-Ibα was performed to quantify endothelial-associated VWF and platelet adhesion. After treatment of wild-type mice for 7 days, aortic molecular signal for endothelial-associated VWF and platelet adhesion were five- to sixfold higher in ponatinib vs sham therapy (P < .001), whereas dasatinib had no effect. In ApoE-/- mice, aortic VWF and platelet signals were two- to fourfold higher for ponatinib-treated compared with sham-treated mice (P < .05) and were significantly higher than in treated wild-type mice (P < .05). Platelet and VWF signals in ponatinib-treated mice were significantly reduced by N-acetylcysteine and completely eliminated by recombinant ADAMTS13. Ponatinib produced segmental left ventricular wall motion abnormalities in 33% of wild-type and 45% of ApoE-/- mice and corresponding patchy perfusion defects, yet coronary arteries were normal on angiography. Instead, a global microvascular angiopathy was detected by immunohistochemistry and by intravital microscopy observation of platelet aggregates and nets associated with endothelial cells and leukocytes. Our findings reveal a new form of vascular toxicity for the TKI ponatinib that involves VWF-mediated platelet adhesion and a secondary microvascular angiopathy that produces ischemic wall motion abnormalities. These processes can be mitigated by interventions known to reduce VWF multimer size.
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Affiliation(s)
| | | | - Melinda Wu
- Knight Cardiovascular Institute
- Doernbecher Children's Hospital, and
| | | | | | - Yue Qi
- Knight Cardiovascular Institute
| | | | | | | | - Toshiaki Shirai
- Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR
| | - Owen J McCarty
- Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR
| | - Zaverio Ruggeri
- Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA
| | - Javid Moslehi
- Cardiovascular Division, Vanderbilt University, Nashville, TN
| | | | - Brian J Druker
- Knight Cancer Institute, Oregon Health & Science University, Portland, OR; and
| | | | - Jonathan R Lindner
- Knight Cardiovascular Institute
- Oregon National Primate Research Center, Oregon Health & Science University, Portland, OR
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Wiernek SL, Jiang B, Gustafson GM, Dai X. Cardiac implications of thrombotic thrombocytopenic purpura. World J Cardiol 2018; 10:254-266. [PMID: 30622684 PMCID: PMC6314883 DOI: 10.4330/wjc.v10.i12.254] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2018] [Revised: 11/20/2018] [Accepted: 11/26/2018] [Indexed: 02/06/2023] Open
Abstract
Thrombotic thrombocytopenic purpura (TTP) is a multisystem disorder that essentially can affect any organ in the human body. The hallmark of the pathogenesis in TTP is the large von Willebrand factor multimers on platelet-mediated micro-thrombi formation, leading to microvascular thrombosis. Autopsy studies showed that cardiac arrest and myocardial infarction are the most common immediate causes of death in these patients. Clinical manifestations of cardiac involvement in TTP vary dramatically, from asymptomatic elevation of cardiac biomarkers, to heart failure, MI and sudden cardiac death. There is limited knowledge about optimal cardiac evaluation and management in patients with TTP. The absence of typical cardiac symptoms, combined with complicated multi-organ involvement in TTP, may contribute to the under-utilization of cardiac evaluation and treatment. Prompt diagnosis and timely initiation of effective therapy could be critically important in selected cases. Based on our experience and this review of the literature, we developed several recommendations for focused cardiac evaluation for patients with acute TTP: (1) patients with suspected or confirmed TTP should be screened for the potential presence of cardiac involvement with detailed history and physical, electrocardiogram and cardiac enzymes; (2) clinical deterioration of TTP patients warrants immediate cardiac reevaluation; (3) TTP patients with clinical evidence of cardiac involvement should be monitored for telemetry, cardiac biomarkers and evaluated with transthoracic echocardiography. These patients require urgent targeted TTP treatment as well as cardiac-specific treatment. Aspirin therapy is indicated for all TTP patients. Since epicardial coronary artery involvement is rare, cardiac catheterization is usually not required, given the high risk for hemorrhage and kidney injury; (4) we recommend evidence-based medical therapy for ischemic symptoms and heart failure. TTP patients with evidence of cardiac involvement would also benefit from routine cardiology follow up during remission.
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Affiliation(s)
- Szymon L Wiernek
- Division of Cardiology, McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States
| | - Bo Jiang
- Division of Cardiology, McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States
| | - Gregory M Gustafson
- Division of Cardiology, Lang Research Center, New York Presbyterian Medical Group – Queens Hospital, Flushing, NY 11355, United States
| | - Xuming Dai
- Division of Cardiology, Lang Research Center, New York Presbyterian Medical Group – Queens Hospital, Flushing, NY 11355, United States
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Cidon EU, Martinez PA, Hickish T. Gemcitabine-induced haemolytic uremic syndrome, although infrequent, can it be prevented: A case report and review of literature. World J Clin Cases 2018; 6:531-537. [PMID: 30397609 PMCID: PMC6212612 DOI: 10.12998/wjcc.v6.i12.531] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2018] [Revised: 09/08/2018] [Accepted: 10/09/2018] [Indexed: 02/05/2023] Open
Abstract
Gemcitabine is an antineoplastic used to treat several malignancies including pancreatic cancer. Its toxicity profile is well known with myelotoxicity, increased vascular permeability and peripheral oedema as most frequent adverse events. However, several cases of acute renal failure have been reported and haemolytic uremic syndrome (HUS) seems to be the underlying process. The cause of HUS remains unknown but its consequences can be lethal. Therefore, a high grade of suspicion is crucial to diagnose it and promptly treat it. This hopefully will reduce its morbidity. HUS is characterized by progressive renal failure associated with microangiopathic haemolytic anaemia and thrombocytopenia. The primary event is damage to endothelial cells and thrombotic microangiopathy (TMA) is the histopathological lesion. TMA affects mainly renal microvasculature. However, some cases evolve with central nervous or cardiovascular systems involvement. We present here a case of gemcitabine-induced HUS, with renal and cardiovascular system affected at the time of diagnosis which to our knowledge this is the first time of such case to be reported.
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Affiliation(s)
- Esther U Cidon
- Department of Medical Oncology, Royal Bournemouth and Christchurch Hospital NHS Foundation Trust, Bournemouth BH7 7DW, United Kingdom
| | - Pilar A Martinez
- Department of Oncology, Clinical University Hospital, Valladolid 47003, Spain
| | - Tamas Hickish
- Department of Medical Oncology, Royal Bournemouth and Christchurch Hospital NHS Foundation Trust and Bournemouth University, Bournemouth BH7 7DW, United Kingdom
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Herbrecht R, Ojeda-Uribe M, Kientz D, Fohrer C, Bohbot A, Hinschberger O, Liu KL, Remy E, Ernst C, Lin JS, Corash L, Cazenave JP. Characterization of efficacy and safety of pathogen inactivated and quarantine plasma in routine use for treatment of acquired immune thrombotic thrombocytopenic purpura. Vox Sang 2018; 113:459-467. [PMID: 29786866 DOI: 10.1111/vox.12663] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2017] [Revised: 04/19/2018] [Accepted: 04/20/2018] [Indexed: 12/18/2022]
Abstract
BACKGROUND Auto-immune thrombotic thrombocytopenic purpura (TTP) is a morbid multi-organ disorder. Cardiac involvement not recognized in initial disease descriptions is a major cause of morbidity. Therapeutic plasma exchange (TPE) requires exposure to multiple plasma donors with risk of transfusion-transmitted infection (TTI). Pathogen inactivation (PI) with amotosalen-UVA, the INTERCEPT Blood System for Plasma (IBSP) is licensed to reduce TTI risk. METHODS An open-label, retrospective study evaluated the efficacy of quarantine plasma (QP) and IBSP in TTP and defined treatment emergent cardiac abnormalities. Medical record review of sequential patient cohorts treated with QP and IBSP characterized efficacy by remission at 30 and 60 days (d) of treatment, time to remission, and volume (L/kg) of plasma required. Safety outcomes focused on cardiac adverse events (AE), relapse rates, and mortality. RESULTS Thirty-one patients (18 IBSP and 13 QP) met study criteria for auto-immune TTP. The proportions (%) of patients in remission at 30 d (IBSP = 61·1, QP = 46·2, P = 0·570) and 60 d (IBSP = 77·8, QP = 76·9, P = 1·00) were not different. Median days to remission were less for IBSP (15·0 vs. 24·0, P = 0·003). Relapse rates (%) 60 d after remission were not different between cohorts (IBSP = 7·1, QP = 40·0, P = 0·150). ECG abnormalities before and during TPE were frequent; however, cardiac AE and mortality were not different between treatment cohorts. CONCLUSIONS Cardiac and a spectrum of ECG findings are common in TTP. In this study, IBSP and QP had similar therapeutic profiles for TPE.
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Affiliation(s)
- R Herbrecht
- Centre de Competence des Microangiopathies d'Alsace, Strasbourg, France
- Hôpitaux Universitaires de Strasbourg, Strasbourg, France
| | - M Ojeda-Uribe
- Centre de Competence des Microangiopathies d'Alsace, Strasbourg, France
- CH Emile Muller, Mulhouse, France
| | | | - C Fohrer
- Centre de Competence des Microangiopathies d'Alsace, Strasbourg, France
- Hôpitaux Universitaires de Strasbourg, Strasbourg, France
| | - A Bohbot
- Hôpitaux Universitaires de Strasbourg, Strasbourg, France
| | | | - K-L Liu
- CH Emile Muller, Mulhouse, France
| | - E Remy
- EFS Alsace, Strasbourg, France
| | - C Ernst
- Cerus Corporation, Concord, CA, USA
| | - J-S Lin
- Cerus Corporation, Concord, CA, USA
| | - L Corash
- Cerus Corporation, Concord, CA, USA
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Dahal S, Ghimire DKC, Sapkota S, Dahal S, Kafle P, Bhandari M. Myocardial Infarction as an Early Presentation in Thrombotic Thrombocytopenic Purpura: A Rare Case Series. J Investig Med High Impact Case Rep 2018; 6:2324709618773789. [PMID: 29761111 PMCID: PMC5946356 DOI: 10.1177/2324709618773789] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2018] [Revised: 03/28/2018] [Accepted: 04/08/2018] [Indexed: 12/22/2022] Open
Abstract
Renal and neurological involvements are frequently seen in thrombotic thrombocytopenic purpura (TTP). Cardiac involvement, however, has been rarely reported. In this article, we present 2 cases of myocardial infarction in patients with TTP. In the first case, a young man presented with non-ST-segment elevation myocardial infarction that resolved promptly with plasmapheresis. The second patient developed ST-segment elevation myocardial infarction early in the course of the disease and died before plasmapheresis could be initiated. Hence, a high degree of suspicion with prompt diagnosis and treatment is needed to prevent mortality associated with cardiac involvement in TTP.
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Affiliation(s)
- Sumit Dahal
- Interfaith Medical Center, Brooklyn, NY, USA
| | | | | | - Suyash Dahal
- KIST Medical College and Teaching Hospital, Lalitpur, Nepal
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31
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Claes KJ, Massart A, Collard L, Weekers L, Goffin E, Pochet JM, Dahan K, Morelle J, Adams B, Broeders N, Stordeur P, Abramowicz D, Bosmans JL, Van Hoeck K, Janssens P, Pipeleers L, Peeters P, Van Laecke S, Levtchenko E, Sprangers B, van den Heuvel L, Godefroid N, Van de Walle J. Belgian consensus statement on the diagnosis and management of patients with atypical hemolytic uremic syndrome. Acta Clin Belg 2018; 73:80-89. [PMID: 29058539 DOI: 10.1080/17843286.2017.1345185] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
- Kathleen J Claes
- Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium
- Laboratory of Nephrology, Department of Microbiology and Immunology, KU Leuven, University of Leuven, Leuven, Belgium
| | - Annick Massart
- Department of Nephrology, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium
| | | | - Laurent Weekers
- Department of Internal Medicine, Division of Nephrology, ULg, CHU Liège, Liège, Belgium
| | - Eric Goffin
- Department of Nephrology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium
| | - Jean-Michel Pochet
- Department of Nephrology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium
| | - Karin Dahan
- Department of Nephrology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium
- Institut de Génétique et de Pathologie, IPG, Gosselies, Belgium
| | - Johann Morelle
- Department of Nephrology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium
| | - Brigitte Adams
- Queen Fabiola Children’s University Hospital, Brussels, Belgium
| | - Nilufer Broeders
- Department of Nephrology, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium
| | - Patrick Stordeur
- Immunobiology Clinic, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium
| | - Daniel Abramowicz
- Department of Nephrology, University Hospital Antwerp, Antwerp, Belgium
| | | | - Koen Van Hoeck
- Department of Pediatrics, University Hospital Antwerp, Antwerp, Belgium
| | - Peter Janssens
- Department of Nephrology and Hypertension, Universitair Ziekenhuis Brussels, Brussels, Belgium
| | - Lissa Pipeleers
- Department of Nephrology and Hypertension, Universitair Ziekenhuis Brussels, Brussels, Belgium
| | - Patrick Peeters
- Department of Nephrology, University Hospital Ghent, Ghent, Belgium
| | | | - Elena Levtchenko
- Department of Pediatric Nephrology, University Hospitals Leuven, Leuven, Belgium
- Department of Development and Regeneration, KU Leuven, Leuven, Belgium
| | - Ben Sprangers
- Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium
- Laboratory of Nephrology, Department of Microbiology and Immunology, KU Leuven, University of Leuven, Leuven, Belgium
| | | | - Nathalie Godefroid
- Pediatric Department, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium
| | - Johan Van de Walle
- Department of Pediatric Nephrology, University Hospital Ghent, Ghent, Belgium
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de Silva NL, Gooneratne L, Wijewickrama E. Acute myocardial infarction associated with thrombotic microangiopathy following a hump-nosed viper bite: a case report. J Med Case Rep 2017; 11:305. [PMID: 29082854 PMCID: PMC5662098 DOI: 10.1186/s13256-017-1484-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2017] [Accepted: 10/07/2017] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Hump-nosed viper bite is the commonest cause of venomous snakebite in Sri Lanka. Despite initially being considered a moderately venomous snake more recent reports have revealed that it could cause significant systemic envenoming leading to coagulopathy and acute kidney injury. However, myocardial infarction was not reported except for a single case, which occurred immediately after the snakebite. CASE PRESENTATION A 50-year-old previously healthy Sri Lankan woman had a hump-nosed viper bite with no evidence of systemic envenoming during initial hospital stay. Five days later she presented with bite site cellulitis with hemorrhagic blisters, acute kidney injury, and evidence of microangiopathic hemolytic anemia and thrombocytopenia with normal coagulation studies. She was managed with supportive care that included intravenously administered antibiotics, blood transfusions, and hemodialysis; both her microangiopathic hemolytic anemia and thrombocytopenia improved without any specific intervention. On day 10 she developed: a non-ST elevation myocardial infarction complicated with acute left ventricular failure evidenced by acute shortness of breath with desaturation despite adequate ultrafiltration; new onset lateral lead T inversions in electrocardiogram; raised troponin I titer; and hypokinetic segments on echocardiogram. She was managed with low molecular weight heparin and antiplatelet drugs, which were later discontinued due to upper gastrointestinal bleeding. Her hospital stay was further complicated by hospital-acquired pneumonia and deep vein thrombosis involving her ileofemoral vein. She died on day 33 from the snakebite. CONCLUSIONS Myocardial infarction after snakebites is rarely reported. This is the first case report of a patient developing a myocardial infarction during the recovery phase of thrombotic microangiopathy following a hump-nosed viper bite. The possibility of thrombotic risk related to thrombotic microangiopathy following hump-nosed viper bite is an area that is poorly studied; it needs further attention.
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Affiliation(s)
| | - Lalindra Gooneratne
- Department of Pathology, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka
| | - Eranga Wijewickrama
- University Medical Unit, National Hospital of Sri Lanka, Colombo, Sri Lanka. .,Department of Clinical Medicine, Faculty of Medicine, University of Colombo, 271, Kynsey road, Colombo 08, Sri Lanka.
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Wiernek SL, Dai X. Obstructive coronary artery disease in patient with acute thrombotic thrombocytopenic purpura. BMJ Case Rep 2017; 2017:bcr2017222437. [PMID: 29038197 PMCID: PMC5652628 DOI: 10.1136/bcr-2017-222437] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/29/2017] [Indexed: 12/22/2022] Open
Abstract
Thrombotic thrombocytopenic purpura (TTP) affects essentially all organ systems. Myocardial injury in TTP is often attributed to microthrombi formation. We present the first case report in the literature of an acute TTP patient with concomitant obstructive coronary artery disease (CAD) and acute myocardial infarction who underwent successful percutaneous coronary intervention (PCI). A 70-year-old female patient who was diagnosed with acute TTP required plasma exchange. The patient also experienced episodes of angina pectoris, elevated cardiac enzymes and global ST segment depressions on ECG. A subsequent non-invasive ischaemia workup revealed significant ischaemia. Coronary angiography revealed obstructive CAD in her right coronary artery, requiring PCI with a bare metal stent placement and dual antiplatelet therapy. The patient tolerated antiplatelet therapy well. At 6 months of follow-up, she had no recurrent angina. This case highlights the potential co-existence of obstructive CAD and acute TTP requiring careful differential diagnosis and treatment.
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Affiliation(s)
- Szymon L. Wiernek
- Division of Cardiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Xuming Dai
- Division of Cardiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
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Noronha N, Costa FD, Dias A, Dinis A. Complement factor B mutation-associated aHUS and myocardial infarction. BMJ Case Rep 2017; 2017:bcr-2017-219716. [PMID: 28710236 DOI: 10.1136/bcr-2017-219716] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
A 6-month-old female infant was referred with a 3-day history of low-grade fever, slight nasal congestion and rhinorrhoea. On admission, the clinical findings were unremarkable and she was discharged home. However, she became progressively more listless with a decreased urine output and was once again seen in the emergency department. Analytically she was found to have metabolic acidosis, hyperkalaemia, thrombocytopaenia, anaemia and schistocytes in the peripheral blood smear. Based on these findings, the diagnosis of haemolyticâ-uremic syndrome was made. A few hours postadmission, there was an abrupt clinical deterioration. She went into cardiorespiratory arrest and she was successfully resuscitated. An ST-segment elevation was noted on the ECG monitor and the troponin I levels were raised, suggesting myocardial infarction. Despite intensive supportive therapy, she went into refractory shock and died within 30 hours.
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Affiliation(s)
- Natália Noronha
- Serviáo de Cuidados Intensivos Pediátricos, Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra, Portugal
| | - Filipa Dias Costa
- Serviáo de Cuidados Intensivos Pediátricos, Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra, Portugal
| | - Andrea Dias
- Serviáo de Cuidados Intensivos Pediátricos, Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra, Portugal
| | - Alexandra Dinis
- Serviáo de Cuidados Intensivos Pediátricos, Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra, Portugal
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35
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von Willebrand factor and its cleaving protease ADAMTS13 balance in coronary artery vessels: Lessons learned from thrombotic thrombocytopenic purpura. A narrative review. Thromb Res 2017; 155:78-85. [DOI: 10.1016/j.thromres.2017.05.011] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2017] [Accepted: 05/11/2017] [Indexed: 02/08/2023]
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36
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Acute myocardial infarction as the initial thrombotic event of thrombotic thrombocytopenic purpura. Blood Coagul Fibrinolysis 2017; 27:948-951. [PMID: 26757016 DOI: 10.1097/mbc.0000000000000513] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Acquired thrombotic thrombocytopenic purpura (TTP) is characterized by the coemergence of microangiopathic hemolytic anemia, thrombocytopenia, and thrombosis-mediated ischemic injuries of various organs, such as the central nervous system and kidneys. Acute myocardial infarction (AMI) has also occasionally been reported as a complication with TTP as the secondary thrombotic event; however, its emergence as the initial thrombotic event in TTP is extremely rare. This report describes an 80-year-old male patient with acquired TTP, who was affected by AMI without any clinically apparent damage to other organs or abnormal laboratory findings that would be suggestive of TTP at the first presentation. Although AMI was successfully treated by percutaneous coronary intervention (PCI), the patient developed marked thrombocytopenia with acute kidney injury and hemolytic anemia 5 days after PCI. The patient was diagnosed as having acquired TTP based on decreased ADAMTS13 (a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13) below the level of detection and the presence of the inhibitor against ADAMTS13, and eventually died of multiorgan failure due to TTP despite undergoing repeated plasma exchanges and immunosuppressive therapies, including corticosteroid and rituximab. Although caution is often paid to therapy-related thrombocytopenia or renal damage after PCI, that is, those caused by antiplatelet drugs, heparin, or contrast agents, our report alerts us to the presence of TTP as an extremely rare, but underlying cause for AMI that could be subclinical at the initial presentation.
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37
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Le Besnerais M, Favre J, Denis CV, Mulder P, Martinet J, Nicol L, Levesque H, Veyradier A, Kopić A, Motto DG, Coppo P, Richard V, Benhamou Y. Assessment of endothelial damage and cardiac injury in a mouse model mimicking thrombotic thrombocytopenic purpura. J Thromb Haemost 2016; 14:1917-1930. [PMID: 27501520 DOI: 10.1111/jth.13439] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2016] [Accepted: 07/18/2016] [Indexed: 01/01/2023]
Abstract
Essentials Endothelial injury is thought to be a key event in thrombotic thrombocytopenic purpura (TTP). Endothelial and cardiac damages were assessed in a model of TTP using ADAMTS-13 knockout mice. Damages of cardiac perfusion and function were associated with nitric oxide pathway alteration. Endothelial dysfunction constitutes a critical event in TTP development and cardiac injury. SUMMARY Background Cardiac alterations represent a major cause of mortality in patients with thrombotic thrombocytopenic purpura (TTP). Endothelial injury remains poorly defined, but seems to be a key initiating event leading to the formation of platelet-rich thrombi in TTP patients. Objectives To assess the changes in endothelial function and the induced cardiac damage in a mouse model of TTP. Patients/methods We used an animal model in which TTP-like symptoms are triggered by injection of 2000 units kg-1 of recombinant von Willebrand factor in ADAMTS-13 knockout mice. Results These mice developed TTP-like symptoms, i.e. severe thrombocytopenia, schistocytosis, and anemia. On day 2, magnetic resonance imaging demonstrated a decrease in left ventricular perfusion associated with alteration of left ventricular ejection fraction, fractional shortening, and cardiac output, suggesting early systolic dysfunction. This was associated with decrease in endothelium-mediated relaxation responses to acetylcholine in mesenteric and coronary arteries, demonstrating severe early endothelial dysfunction. In parallel, we showed decreased cardiac expression of endothelial nitric oxide (NO) synthase and increased expression of antioxidant enzymes, suggesting alteration of the NO pathway. At this time, cardiac immunohistochemistry revealed an increase in the expression of VCAM-1 and E-selectin. Conclusion This study provides evidence that the heart is a sensitive target organ in TTP, and shows, for the first time, strong mesenteric and coronary endothelial dysfunction in an induced-TTP model. The mechanisms incriminated are the occurrence of a pro-oxidant state, and proadhesive and proinflammatory phenotypes. This previously largely unrecognized vascular dysfunction may represent an important contributor to the systemic organ failure occurring in TTP.
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Affiliation(s)
- M Le Besnerais
- Service de Médecine Interne, CHU Charles Nicolle, Rouen, France
- INSERM U1096, UFR médecine pharmacie Rouen, Rouen, France
- Centre de Référence des Microangiopathies Thrombotiques, Hôpital Saint-Antoine, AP-HP, Paris, France
| | - J Favre
- INSERM U1096, UFR médecine pharmacie Rouen, Rouen, France
| | - C V Denis
- INSERM UMR S 1176, Université Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France
| | - P Mulder
- INSERM U1096, UFR médecine pharmacie Rouen, Rouen, France
| | - J Martinet
- INSERM U905, UFR médecine pharmacie Rouen, Rouen, France
| | - L Nicol
- INSERM U1096, UFR médecine pharmacie Rouen, Rouen, France
| | - H Levesque
- Service de Médecine Interne, CHU Charles Nicolle, Rouen, France
- INSERM U1096, UFR médecine pharmacie Rouen, Rouen, France
| | - A Veyradier
- Service d'hématologie biologique, Hôpital Lariboisière, AP-HP, Paris, France
- EA3518, IUH Saint Louis, Université Paris-Diderot, Paris, France
| | - A Kopić
- Baxalta Innovations GmbH, Vienna, Austria
| | - D G Motto
- Bloodworks Northwest Research Institute, Seattle, WA, USA
| | - P Coppo
- Centre de Référence des Microangiopathies Thrombotiques, Hôpital Saint-Antoine, AP-HP, Paris, France
- Service d'Hématologie, Hôpital Saint-Antoine, AP-HP, Paris, France
- Institut Gustave Roussy, INSERM U1170, Villejuif, France
| | - V Richard
- INSERM U1096, UFR médecine pharmacie Rouen, Rouen, France
| | - Y Benhamou
- Service de Médecine Interne, CHU Charles Nicolle, Rouen, France.
- INSERM U1096, UFR médecine pharmacie Rouen, Rouen, France.
- Centre de Référence des Microangiopathies Thrombotiques, Hôpital Saint-Antoine, AP-HP, Paris, France.
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Mouabbi JA, Zein R, Kafri Z, Al-Katib A, Hadid T. Thrombotic thrombocytopenic purpura presenting as acute coronary syndrome. Clin Case Rep 2016; 4:736-9. [PMID: 27525072 PMCID: PMC4974416 DOI: 10.1002/ccr3.606] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2015] [Revised: 04/23/2016] [Accepted: 05/24/2016] [Indexed: 11/29/2022] Open
Abstract
In patients presenting with thrombotic thrombocytopenia purpura and non‐ST elevation myocardial infarction, prompt initiation of plasma exchange takes precedence over other invasive diagnostic procedures for coronary artery disease. Such procedures should be delayed until clinical condition and laboratory parameters have been stabilized.
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Affiliation(s)
- Jason Aboudi Mouabbi
- Internal Medicine St John Hospital and Medical Center Grosse Pointe Woods Michigan USA
| | - Rami Zein
- Internal Medicine St John Hospital and Medical Center Grosse Pointe Woods Michigan USA
| | - Zyad Kafri
- Van Elslander Cancer Center St John Hospital & Medical Center Grosse Pointe Woods Michigan USA
| | - Ayad Al-Katib
- Hematology Oncology St John Hospital and Medical Center Grosse Pointe Woods Michigan USA
| | - Tarik Hadid
- Van Elslander Cancer Center St John Hospital & Medical Center Grosse Pointe Woods Michigan USA
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Abstract
Post-infectious hemolytic uremic syndrome (HUS) is caused by specific pathogens in patients with no identifiable HUS-associated genetic mutation or autoantibody. The majority of episodes is due to infections by Shiga toxin (Stx) producing Escherichia coli (STEC). This chapter reviews the epidemiology and pathogenesis of STEC-HUS, including bacterial-derived factors and host responses. STEC disease is characterized by hematological (microangiopathic hemolytic anemia), renal (acute kidney injury) and extrarenal organ involvement. Clinicians should always strive for an etiological diagnosis through the microbiological or molecular identification of Stx-producing bacteria and Stx or, if negative, serological assays. Treatment of STEC-HUS is supportive; more investigations are needed to evaluate the efficacy of putative preventive and therapeutic measures, such as non-phage-inducing antibiotics, volume expansion and anti-complement agents. The outcome of STEC-HUS is generally favorable, but chronic kidney disease, permanent extrarenal, mainly cerebral complication and death (in less than 5 %) occur and long-term follow-up is recommended. The remainder of this chapter highlights rarer forms of (post-infectious) HUS due to S. dysenteriae, S. pneumoniae, influenza A and HIV and discusses potential interactions between these pathogens and the complement system.
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Affiliation(s)
- Denis F. Geary
- Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario Canada
| | - Franz Schaefer
- Division of Pediatric Nephrology, University of Heidelberg, Heidelberg, Germany
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Thejeel B, Garg AX, Clark WF, Liu AR, Iansavichus AV, Hildebrand AM. Long-term outcomes of thrombotic microangiopathy treated with plasma exchange: A systematic review. Am J Hematol 2016; 91:623-30. [PMID: 26910131 DOI: 10.1002/ajh.24339] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2016] [Accepted: 02/17/2016] [Indexed: 12/12/2022]
Abstract
With the adoption of plasma exchange as standard treatment for thrombotic microangiopathy (TMA), more patients are surviving and long-term outcomes have greater relevance. We conducted a systematic review to synthesize and evaluate the quality of evidence on long-term outcomes of TMA among adults treated with plasma exchange and to identify factors that may be associated with a worse long-term prognosis. We searched databases from 1980 to 2013 for eligible articles published in any language. We included studies that reported outcomes in at least ten adults with a history of TMA treated with plasma exchange and at least 6 months of follow-up. We abstracted data in duplicate and assessed the methodological quality of each study using an assessment tool developed based on recommended validity criteria. We screened 6672 articles, reviewed 213, and included 34 studies totaling 1182 patients (study median [range], 24 [10-118]). The mean (or median) follow-up ranged from 6 months to 13 years. The cumulative incidence of relapse and mortality was highly variable and ranged from 3 to 84 and 0 to 61%, respectively. The incidence of other outcomes across 10 studies also varied (outcomes included hypertension, kidney disease, preeclampsia, stroke, seizure, severe cognitive impairment, and depression); in three other studies, long-term neurocognitive function and health-related quality of life were significantly lower than in the general population. Patients who survive an episode of TMA may be susceptible to long-term vascular complications, but the magnitude of this risk and how to mitigate it remains unclear. Am. J. Hematol. 91:623-630, 2016. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Bashiar Thejeel
- Schulich School of Medicine, Western University, London, Ontario, Canada
- Kidney Clinical Research Unit, London Health Sciences Centre, London, Ontario, Canada
| | - Amit X Garg
- Kidney Clinical Research Unit, London Health Sciences Centre, London, Ontario, Canada
- Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada
- Division of Nephrology, Western University, London, Ontario, Canada
| | - William F Clark
- Kidney Clinical Research Unit, London Health Sciences Centre, London, Ontario, Canada
- Division of Nephrology, Western University, London, Ontario, Canada
| | - Aiden R Liu
- Kidney Clinical Research Unit, London Health Sciences Centre, London, Ontario, Canada
| | - Arthur V Iansavichus
- Kidney Clinical Research Unit, London Health Sciences Centre, London, Ontario, Canada
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Peyvandi F, Scully M, Kremer Hovinga JA, Cataland S, Knöbl P, Wu H, Artoni A, Westwood JP, Mansouri Taleghani M, Jilma B, Callewaert F, Ulrichts H, Duby C, Tersago D. Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura. N Engl J Med 2016; 374:511-22. [PMID: 26863353 DOI: 10.1056/nejmoa1505533] [Citation(s) in RCA: 450] [Impact Index Per Article: 50.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
BACKGROUND Acquired thrombotic thrombocytopenic purpura (TTP) is caused by aggregation of platelets on ultralarge von Willebrand factor multimers. This microvascular thrombosis causes multiorgan ischemia with potentially life-threatening complications. Daily plasma exchange and immunosuppressive therapies induce remission, but mortality and morbidity due to microthrombosis remain high. METHODS Caplacizumab, an anti-von Willebrand factor humanized single-variable-domain immunoglobulin (Nanobody), inhibits the interaction between ultralarge von Willebrand factor multimers and platelets. In this phase 2, controlled study, we randomly assigned patients with acquired TTP to subcutaneous caplacizumab (10 mg daily) or placebo during plasma exchange and for 30 days afterward. The primary end point was the time to a response, defined as confirmed normalization of the platelet count. Major secondary end points included exacerbations and relapses. RESULTS Seventy-five patients underwent randomization (36 were assigned to receive caplacizumab, and 39 to receive placebo). The time to a response was significantly reduced with caplacizumab as compared with placebo (39% reduction in median time, P=0.005). Three patients in the caplacizumab group had an exacerbation, as compared with 11 patients in the placebo group. Eight patients in the caplacizumab group had a relapse in the first month after stopping the study drug, of whom 7 had ADAMTS13 activity that remained below 10%, suggesting unresolved autoimmune activity. Bleeding-related adverse events, most of which were mild to moderate in severity, were more common with caplacizumab than with placebo (54% of patients vs. 38%). The frequencies of other adverse events were similar in the two groups. Two patients in the placebo group died, as compared with none in the caplacizumab group. CONCLUSIONS Caplacizumab induced a faster resolution of the acute TTP episode than did placebo. The platelet-protective effect of caplacizumab was maintained during the treatment period. Caplacizumab was associated with an increased tendency toward bleeding, as compared with placebo. (Funded by Ablynx; ClinicalTrials.gov number, NCT01151423.).
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Affiliation(s)
- Flora Peyvandi
- From the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (F.P., A.A.), and the Department of Pathophysiology and Transplantation, University of Milan (F.P.) - both in Milan, Italy; the Department of Haematology, University College London Hospital (M.S., J.-P.W.), and the National Institute for Health Research Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London (M.S.) - both in London, U.K.; the University Clinic of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital and the University of Bern - both in Bern, Switzerland (J.A.K.H., M.M.T.); the Departments of Internal Medicine (S.C.) and Pathology (H.W.), Ohio State University, Columbus; the Departments of Medicine, Division of Hematology and Hemostasis (P.K.), and Clinical Pharmacology (B.J.), Medical University of Vienna, Vienna, Austria; and the Departments of Clinical Development (F.C., C.D., D.T.) and Pharmacology (H.U.), Ablynx, Zwijnaarde, Belgium
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Oshima T, Ikutomi M, Shinohara H, Ishiwata J, Fukino K, Amaki T, Nakamura F. Acute Myocardial Infarction Caused by Thrombotic Microangiopathy Complicated With Myelodysplastic Syndrome. Int Heart J 2016; 57:634-6. [DOI: 10.1536/ihj.16-100] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Affiliation(s)
- Tsukasa Oshima
- Third Department of Internal Medicine, Teikyo University Chiba Medical Center
| | - Masayasu Ikutomi
- Third Department of Internal Medicine, Teikyo University Chiba Medical Center
| | - Hiroki Shinohara
- Third Department of Internal Medicine, Teikyo University Chiba Medical Center
| | - Jumpei Ishiwata
- Third Department of Internal Medicine, Teikyo University Chiba Medical Center
| | - Keiko Fukino
- Third Department of Internal Medicine, Teikyo University Chiba Medical Center
| | - Toshihiro Amaki
- Third Department of Internal Medicine, Teikyo University Chiba Medical Center
| | - Fumitaka Nakamura
- Third Department of Internal Medicine, Teikyo University Chiba Medical Center
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Tasaki T, Yamada S, Nabeshima A, Noguchi H, Nawata A, Hisaoka M, Sasaguri Y, Nakayama T. An autopsy case of myocardial infarction due to idiopathic thrombotic thrombocytopenic purpura. Diagn Pathol 2015; 10:52. [PMID: 26022055 PMCID: PMC4446843 DOI: 10.1186/s13000-015-0285-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2015] [Accepted: 04/22/2015] [Indexed: 01/16/2023] Open
Abstract
UNLABELLED Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder characterized by systemic platelet-von Willebrand factor aggregation, organ ischemia and profound thrombocytopenia. In this report, we describe an autopsy case of a 77-year-old Japanese man diagnosed with idiopathic TTP. He had no history of cardiovascular disease symptoms, such as chest pain, ST segment elevation, and elevation of cardiac enzyme levels, except arrhythmia. The patient suddenly died despite receiving many treatments. On autopsy, macroscopically and microscopically, acute and chronic myocardial infarction manifested as petechiae and fibrotic foci and covered a wide area in the myocardium, including the area near the atrioventricular node. The microthrombi in the small arterioles and capillaries were platelet thrombi, which showed positive results for periodic acid-Schiff stain and factor VIII on immunohistochemical staining. The cause of the sudden death was suspected to be myocardial infarction, including a cardiac conduction system disorder due to multiple platelet microthrombi. Asymptomatic myocardial infarction is an important cause of death in TTP. Therefore, the heart tissue, including the sinus-atrial node and the atrioventricular node, should be microscopically examined more closely in autopsy cases of patients with TTP who experienced sudden death of TTP. This report is a critical teaching case considering that its cause of sudden death may be arrhythmia due to a myocardial infarction including cardiac conduction system disorder by platelet microthrombi. VIRTUAL SLIDES The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2113354005156739.
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Affiliation(s)
- Takashi Tasaki
- Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.
| | - Sohsuke Yamada
- Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.
| | - Atsunori Nabeshima
- Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.
| | - Hirotsugu Noguchi
- Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.
| | - Aya Nawata
- Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.
| | - Masanori Hisaoka
- Pathology and Oncology, University of Occupational and Environmental Health, Kitakyusyu, Japan.
| | | | - Toshiyuki Nakayama
- Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.
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Sauvètre G, Grange S, Froissart A, Veyradier A, Coppo P, Benhamou Y. La révolution des anticorps monoclonaux dans la prise en charge des microangiopathies thrombotiques. Rev Med Interne 2015; 36:328-38. [DOI: 10.1016/j.revmed.2014.10.364] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2014] [Revised: 08/22/2014] [Accepted: 10/24/2014] [Indexed: 12/15/2022]
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Benhamou Y, Boelle PY, Baudin B, Ederhy S, Gras J, Galicier L, Azoulay E, Provôt F, Maury E, Pène F, Mira JP, Wynckel A, Presne C, Poullin P, Halimi JM, Delmas Y, Kanouni T, Seguin A, Mousson C, Servais A, Bordessoule D, Perez P, Hamidou M, Cohen A, Veyradier A, Coppo P. Cardiac troponin-I on diagnosis predicts early death and refractoriness in acquired thrombotic thrombocytopenic purpura. Experience of the French Thrombotic Microangiopathies Reference Center. J Thromb Haemost 2015; 13:293-302. [PMID: 25403270 DOI: 10.1111/jth.12790] [Citation(s) in RCA: 105] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2014] [Indexed: 08/31/2023]
Abstract
BACKGROUND Cardiac involvement is a major cause of mortality in patients with thrombotic thrombocytopenic purpura (TTP). However, diagnosis remains underestimated and delayed, owing to subclinical injuries. Cardiac troponin-I measurement (cTnI) on admission could improve the early diagnosis of cardiac involvement and have prognostic value. OBJECTIVES To assess the predictive value of cTnI in patients with TTP for death or refractoriness. PATIENTS/METHODS The study involved a prospective cohort of adult TTP patients with acquired severe ADAMTS-13 deficiency (< 10%) and included in the registry of the French Reference Center for Thrombotic Microangiopathies. Centralized cTnI measurements were performed on frozen serum on admission. RESULTS Between January 2003 and December 2011, 133 patients with TTP (mean age, 48 ± 17 years) had available cTnI measurements on admission. Thirty-two patients (24%) had clinical and/or electrocardiogram features. Nineteen (14.3%) had cardiac symptoms, mainly congestive heart failure and myocardial infarction. Electrocardiogram changes, mainly repolarization disorders, were present in 13 cases. An increased cTnI level (> 0.1 μg L(-1) ) was present in 78 patients (59%), of whom 46 (59%) had no clinical cardiac involvement. The main outcomes were death (25%) and refractoriness (17%). Age (P = 0.02) and cTnI level (P = 0.002) showed the greatest impact on survival. A cTnI level of > 0.25 μg L(-1) was the only independent factor in predicting death (odds ratio [OR] 2.87; 95% confidence interval [CI] 1.13-7.22; P = 0.024) and/or refractoriness (OR 3.03; 95% CI 1.27-7.3; P = 0.01). CONCLUSIONS A CTnI level of > 0.25 μg L(-1) at presentation in patients with TTP appears to be an independent factor associated with a three-fold increase in the risk of death or refractoriness. Therefore, cTnI level should be considered as a prognostic indicator in patients diagnosed with TTP.
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Affiliation(s)
- Y Benhamou
- Service de Médecine Interne, CHU Charles Nicolle, Rouen, France; Inserm U1096, Rouen, France; Centre de Référence des Microangiopathies Thrombotiques, Hôpital Saint-Antoine, AP-HP, Paris, France
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Tuter DS, Kopylov FY, Kozlovskaya NL, Demyanova KA, Shchekochikhin DY, Shilov EM, Syrkin AL. Cardiac involvement in thrombotic microangiopathies. TERAPEVT ARKH 2015; 87:17-25. [DOI: 10.17116/terarkh201587917-25] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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Nichols L, Berg A, Rollins-Raval MA, Raval JS. Cardiac Injury Is a Common Postmortem Finding in Thrombotic Thrombocytopenic Purpura Patients: Is Empiric Cardiac Monitoring and Protection Needed? Ther Apher Dial 2014; 19:87-92. [DOI: 10.1111/1744-9987.12191] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Larry Nichols
- Department of Pathology; University of Pittsburgh Medical Center
| | - Aaron Berg
- Department of Pathology; University of Pittsburgh Medical Center
| | | | - Jay S Raval
- Department of Pathology; University of Pittsburgh Medical Center
- The Institute for Transfusion Medicine; Pittsburgh PA USA
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Camous L, Veyradier A, Darmon M, Galicier L, Mariotte E, Canet E, Parquet N, Azoulay É. Macrovascular thrombosis in critically ill patients with thrombotic micro-angiopathies. Intern Emerg Med 2014; 9:267-72. [PMID: 23054401 DOI: 10.1007/s11739-012-0851-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2012] [Accepted: 09/14/2012] [Indexed: 12/24/2022]
Abstract
The purpose of this study is to assess the incidence and describe the clinical and pathological features of macrovascular thrombosis during the course of thrombotic micro-angiopathy (TMA) in a 6 year retrospective study of all adults with TMA, admitted to a teaching-hospital ICU. Of the 55 patients identified, all had anaemia and thrombocytopenia and 45 (82 %) had renal or neurological impairment. All patients received plasmapheresis, steroids, and strict blood pressure control. Macrovascular venous or arterial thromboses were diagnosed in 28 (51 %) patients; among them, 7 had cerebral artery thrombosis and 21 (including 13 with central venous catheters) had deep vein thrombosis. Median time from plasmapheresis initiation to thrombosis was 7 (4-10) days. Clinical findings were suggestive of deep venous thrombosis in 7 of the 21 patients (33 %) and only one of the 7 patients with stroke had corresponding clinical signs. By multivariate analysis, factors independently associated with macrovascular thrombosis were undetectable ADAMTS13 activity (odds ratio 7.33, 95 % confidence interval 1.3-41.3), cardiac involvement with TMA (odds ratio, 3.46; 95 % confidence interval, 1.1-13.9) and TMA flare (odds ratio 9.03; 95 % confidence interval 1.03-79.4). In conclusion, half of the patients with TMA experience macrovascular thrombosis. Patients with TTP-related ADAMTS13 deficiency and those with cardiac manifestations of TMA are at higher risk for arterial or deep venous thrombosis.
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Affiliation(s)
- Laurent Camous
- Medical ICU, Clinical Immunology and Hemapheresis Departments, AP-HP, Hôpital Saint-Louis, 1 Avenue Claude Vellefaux, 75010, Paris, France
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Noris M, Remuzzi G. Cardiovascular complications in atypical haemolytic uraemic syndrome. Nat Rev Nephrol 2014; 10:174-80. [DOI: 10.1038/nrneph.2013.280] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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Doll JA, Kelly JP. ST-segment elevation myocardial infarction treated with thrombolytic therapy in a patient with thrombotic thrombocytopenic purpura. J Thromb Thrombolysis 2013; 38:124-6. [DOI: 10.1007/s11239-013-1018-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
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